The purpose of this project is to define the regulatory mechanisms which control purine biosynthesis and the renal excretion of uric acid. Study of the regulatory mechanisms which control purine biosynthesis will be approached on three levels: a) Evaluation of the kinetic and physical properties of amidophosphoribosyltransferase, the enzyme which catalyzes the first reaction unique to the pathway of purine biosynthesis. b) Study of the control of purine biosynthesis in normal fibroblasts and hepatocytes. Purine biosynthesis will also be studied in cells with a mutant form of amidophosphoribosyltransferase which has abnormal kinetic properties. c) Study of purine metabolism in patients with gout. The studies regarding the control of uric acid excretion by the kidney are designed to identify and characterize circulating factors which influence urate handling by the kidney. These experiments will make use of a genetic model, the Dalmatian coach hound, since a circulating factor is thought to be responsible for the defect in urate reabsorption in the Dalmatian kidney. The control of purine biosynthesis and renal excretion of uric acid have direct application to patients with gout because an abnormality in either one or both of these control processes is responsible for the production of hyperuricemia in these patients.